Blood basophils are prominent at numerous delayed-onset immune inflammatory reaction sites. These cells contain several pharmacologically active mediators which are known to elicit inflammatory reactions and control immune responses. We have shown that cell-free supernatants from cultured human mononuclear cells, stimulated with mitogens or recall antigens induce the release of histamine from basophils. The physical and chemical properties of this low molecular weight (12,000 dalton) protein are being investigated. The effect of this factor(s) and the mechanisms resulting in histamine release will be compared with the data obtained for antigen-IgE and complement fragment induced release of histamine from basophils. In addition, the cell-type(s) and sub-sets of cells producing HRA, the time of production and possible role of helper cells in the initiation of production are being determined. We are also attempting to correlate skin tests with antigens and various mitogens to the in-vitro production of the releasing activity. These data should help us to understand the role of basophils in the elicitation and regulation of cell-mediated reactions.